Variant 6-83853441-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001009994.3(RIPPLY2):c.25G>C(p.Gly9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,391,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

RIPPLY2
NM_001009994.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.20

Variant links:

Genes affected

RIPPLY2 (HGNC:21390): (ripply transcriptional repressor 2) This gene encodes a nuclear protein that belongs to a novel family of proteins required for vertebrate somitogenesis. Members of this family have a tetrapeptide WRPW motif that is required for interaction with the transcriptional repressor Groucho and a carboxy-terminal Ripply homology domain/Bowline-DSCR-Ledgerline conserved region required for transcriptional repression. Null mutant mice die soon after birth and display defects in axial skeleton segmentation due to defective somitogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

RIPPLY2 links:

ENSG00000287705 (HGNC:):

ENSG00000287705 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049293905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPPLY2	NM_001009994.3 link	c.25G>C	p.Gly9Arg	missense_variant	1/4	ENST00000369689.6	NP_001009994.1	Q5TAB7-1
RIPPLY2	NM_001400900.1 link	c.25G>C	p.Gly9Arg	missense_variant	1/3		NP_001387829.1
RIPPLY2-CYB5R4	NR_174604.1 link	n.82G>C		non_coding_transcript_exon_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPPLY2	ENST00000369689.6 link	c.25G>C	p.Gly9Arg	missense_variant	1/4	1	NM_001009994.3	ENSP00000358703.1		Q5TAB7-1
ENSG00000287705	ENST00000656981.1 link	n.727C>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000287

AC:

AN:

1391652

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

686598

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000371

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 10, 2024

The c.25G>C (p.G9R) alteration is located in exon 1 (coding exon 1) of the RIPPLY2 gene. This alteration results from a G to C substitution at nucleotide position 25, causing the glycine (G) at amino acid position 9 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.1

DANN

Benign

0.78

DEOGEN2

Benign

0.12

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.38

M_CAP

Benign

0.036

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.070

REVEL

Benign

0.032

Sift

Benign

0.35

Sift4G

Benign

0.87

Polyphen

0.0010

Vest4

0.070

MutPred

0.10

Loss of catalytic residue at G9 (P = 0.0185);

MVP

0.22

MPC

0.11

ClinPred

0.19

GERP RS

-2.1

Varity_R

0.070

gMVP

0.044

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over